Basic insights into Zika virus infection of neuroglial and brain endothelial cells

Abstract

<jats:p>Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain–Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood–brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood. This study characterizes the <jats:italic>in vitro</jats:italic> infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). Readouts included infection kinetics, intracellular virus localization, viral persistence and cytokine responses. Although not as high as in Vero cells, viral titres exceeded 10<jats:sup>4</jats:sup> plaque-forming units (p.f.u.) ml<jats:sup>−1</jats:sup> in the endothelial/neuroglial cell types, except hOECs. Despite these substantial titres, a relatively small proportion of neuroglial cells were primarily infected. Immunolabelling of infected cells revealed localization of the ZIKV envelope and NS3 proteins in the cytoplasm; NS3 staining overlapped with that of dsRNA replication intermediate and the endoplasmic reticulum (ER). Infected OECs and endothelial cells produced high levels of pro-inflammatory chemokines. Nevertheless, ZIKV was also able to establish persistent infection in hOEC and hCMEC/D3 cells. Taken together, these results provide basic insights into ZIKV infection of endothelial and neuroglial cells and will form the basis for further study of ZIKV disease mechanisms.</jats:p>

SARS-CoV-2 Structural Proteins Exposure Alter Thrombotic and Inflammatory Responses in Human Endothelial Cells

“… 37 Similarly, after 10 days of exposure to Zika virus, brain endothelial cells (hCMECs) did not show a reduction in cell viability. 34 After a 6 day exposure to the Coxsackie virus, HUVECs did not respond with a change in their cell density, morphology or any other culture parameters investigated. 6 Overall, our data is generally in agreement with these prior reports and illustrates that a short duration exposure to SARS-CoV-2 structural proteins does not impair endothelial cell viability and density (with the exception of N-protein).…”

Non-permissive SARS-CoV-2 infection in human neurospheres

“…SARS-CoV-2 infection has been associated with cytokine storm as a poor prognosis of disease progression ( Tay et al, 2020 ). Misbalance of cytokine levels in the CNS microenvironment is associated with several pathologies ( Guzman-Martinez et al, 2019 , Lima et al, 2019 , Mutso et al, 2020 , Sochocka et al, 2017 ), hence the need to uncover the brain inflammation associated with SARS-CoV-2 infection. To investigate if SARS-CoV-2 generates a direct inflammatory response in neural tissues, the supernatant of infected NP was collected at 5 d.p.i.…”

Tracking the Replication-Competent Zika Virus with Tetracysteine-Tagged Capsid Protein in Living Cells

“…This piece of evidence is in agreement with a recent study that found that the process of ZIKV crossing the hCMEC/D3 cell-monolayer was blocked by pharmacological inhibitors of endocytosis ( 41 ). Recent studies found that ZIKV establishes persistent infection in the BBB model cell line hCMEC/D3 ( 42 ). Interestingly, ZIKV infection fails to damage the hCMEC/D3 cells ( 42 , 43 ).…”